DESCRIPTION(Provided by applicant): The major focus of this research addresses molecular mechanisms that underlie protein synthesis-dependent plasticity. In particular, this proposal is aimed at characterizing properties of the immediate early gene(IEG) Narp (Neuronal Activity Regulated Pentraxin). Narp was identified as a protein of interest based on its rapid induction in brain in response to seizure stimulation. While no specific functional role for Narp has yet been established, several lines of evidence indicate this protein may participate in excitatory synaptogenesis. Narp co-localizes with certain subtypes of AMPA receptors at axo-dendritic synapses. Narp and GluR1 Coimmunoprecipitate from brain suggesting a physiological interaction between these two proteins. Furthermore, transient up-regulation of Narp enhances AMPA Receptor cluster formation as well as excitatory synapse density. Narp is a 432 amino acid protein that self-associates in a multimeric fashion. Analysis of Narp's amino acid sequence has revealed several putative coiled coil domains, Ca2+ binding sites, and a high degree of homology to the pentraxin family of secreted lectins. The specific goals of this thesis project are to elucidate a structure-function relationship between Narp and the AMPA Receptor, to study mechanims of regulated Narp secretion, and to further characterize the role of Narp in excitatory synaptogenesis.